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Abstract

In chapter one, hepatocyte growth factor HGF, its receptor, the tyrosine kinase Met and their
biological implications are introduced, and the structure and role of the glycosaminoglycans
(GAGs) heparan sulfate and heparin are described. An account of the previous work on the
project is given, setting aims for this project.
In chapter two, the syntheses of the two best compounds of the first generation of mimics is
described, thereby resolving the structural ambiguities of those compounds. An efficient
sulfation methodology is described. Docking results for the two mimics to NK1 using AutoDock
Vina are reported.
In chapter three, the design of a new generation of compounds is described, based on
conformational restrictions: results of a virtual screen of 36 compounds are reported along with
a newly written script for automated virtual screening.
In chapter four, efforts towards the synthesis of 2-substituted chroman derivatives are
described: an easy two-step methodology for the preparation of chroman-2-ones is described,
from which a three-step sequence allows access to various 2-substituted chromans.
In chapter five, efforts towards the synthesis of 3- and 4-substituted chroman derivatives are
described.
In chapter six, attempts to apply the 2-substituted chroman derivative prepared in chapter four
to the total synthesis of erythrococcamide B are described. A new one-step methodology for
the preparation of 2-allyl chroman derivatives from chroman-2-ones, via reductive allylation
using EtsSiH-lnBrs-allylTMS, is reported with its application to the synthesis of
Erythrococcamide B.
In chapter seven, conclusions are drawn and directions for future work proposed.
Roman LAGOUTTE - PhD Thesis - Salford 2010